SurVaxM missed the SURVIVE trial OS end point in newly diagnosed glioblastoma, whereas a subgroup of patients 65 or younger had significantly improved OS.
The novel cancer vaccine SurVaxM generated a clinically meaningful OS improvement vs placebo in patients with newly diagnosed glioblastoma in the phase 2b SURVIVE trial (NCT05163080), although the trial did not reach statistical significance for the primary end point of OS.1
Among 233 evaluable patients across both arms, the median OS was 22.8 months with SurVaxM vs 20.3 months with placebo (HR, 0.75; 95% CI, 0.54-1.03; P = .076). In a prespecified subgroup of patients ages 65 years or younger, the median OS values were 24.2 months vs 20.2 months, respectively, translating to a statistically significant benefit with the vaccine (HR, 0.64; 95% CI, 0.44-0.93; P = .019). Both OS analyses were adjusted for MGMT status and Karnofsky performance status stratification factors.
SurVaxM is an investigational, first-in-class peptide-mimic vaccine that targets survivin and is given by subcutaneous injection. The agent has been granted FDA orphan drug and fast track designations for the treatment of patients with newly diagnosed glioblastoma.
“Every patient with glioblastoma is facing one of the hardest diagnoses in medicine,” Ajay Abad, MD, the principal investigator of SURVIVE, stated in a news release. “To see many of our study patients living longer, and several of them living years longer, is deeply meaningful to every one of us who has participated in the work to develop and study this new treatment approach. An improvement in survival of this magnitude is noteworthy.”
Abad is an assistant professor of oncology and neurology in the Department of Neuro-Oncology at Roswell Park in Buffalo, New York.
SurVaxM Plus Standard Therapy in Newly Diagnosed Glioblastoma: SURVIVE Highlights
SURVIVE is a randomized, double-blind, placebo-controlled, multicenter trial that added SurVaxM or placebo to standard-of-care temozolomide (Temodar) in patients with newly diagnosed glioblastoma.2 Patients in the SurVaxM arm received a subcutaneous injection of SurVaxM in Montanide plus a separate injection of sargramostim (Leukine) at the same site, whereas patients in the control arm received saline in Montanide and a saline injection in place of sargramostim; injections were repeated on a set schedule.
Eligible patients had pathologically confirmed glioblastoma of the cerebrum, a Karnofsky performance status of 70 or higher, and available MGMT methylation and IDH1 mutation results. Patients needed to have completed radiotherapy with at least 75% of concurrent temozolomide per the Stupp protocol, shown no disease progression after chemoradiation, and be randomly assigned within 16 weeks of resection. A postoperative MRI within 72 hours of surgery needed to show gross total resection or residual enhancement of 1 cm³ or less. Patients who elected to undergo tumor treating fields, or who had received prior immunotherapy or bevacizumab (Avastin), were excluded.
OS was the primary end point. Secondary end points included progression-free survival (PFS), OS and PFS at prespecified time points, and grade 3 or 4 toxicities. The analysis included evaluable patients from 11 United States cancer centers.
In the subgroup of patients 65 years or younger, a PFS benefit was seen with SurVaxM (HR, 0.64; P = .018), and the 12-month PFS rate was 44% with SurVaxM vs 24% with placebo.¹ Approximately 42% of patients in the SurVaxM arm were alive at 30 months or later vs 18% of those in the placebo arm, and no further deaths were reported between 30 and 54 months.
Adverse effects (AEs) in the SurVaxM arm were mostly grade 1 or 2, including injection-site reaction (48%), pain (41%), erythema (39%), pruritus (38%), and swelling (29%). Influenza-like illness occurred in 13% of patients in this arm. Grade 3 or higher AEs occurred in 48% of patients receiving SurVaxM vs 46% of those receiving placebo, and serious AEs occurred in 25% vs 21% of patients, respectively. Treatment discontinuation because of AEs occurred in 4% of patients in the SurVaxM arm, with 1 discontinuation attributed to study treatment. No treatment-related deaths occurred in either arm.
MimiVax, the developer of SurVaxM, plans to meet with the FDA in the coming months to review the data and determine a path forward, including discussion of breakthrough therapy designation and other expedited pathways, such as accelerated approval. SurVaxM is also being evaluated in patients with neuroendocrine tumors, multiple myeloma, and pediatric brain cancers.
